Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTL935N)

• DTT Name: Proteinase activated receptor 1 (F2R)
• Synonyms: Thrombin receptor; Proteinase-activated receptor 1; Protease-activated receptor-1; Protease activated receptor 1; PAR1; PAR-1; Coagulation factor II receptor; CF2R
• Gene Name: F2R
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: PAR1_HUMAN
• TTD ID: T36483
• Sequence:
  MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPRSFLLRNPNDKYEPFWEDEE
  KNESGLTEYRLVSINKSSPLQKQLPAFISEDASGYLTSSWLTLFVPSVYTGVFVVSLPLN
  IMAIVVFILKMKVKKPAVVYMLHLATADVLFVSVLPFKISYYFSGSDWQFGSELCRFVTA
  AFYCNMYASILLMTVISIDRFLAVVYPMQSLSWRTLGRASFTCLAIWALAIAGVVPLLLK
  EQTIQVPGLNITTCHDVLNETLLEGYYAYYFSAFSAVFFFVPLIISTVCYVSIIRCLSSS
  AVANRSKKSRALFLSAAVFCIFIICFGPTNVLLIAHYSFLSHTSTTEAAYFAYLLCVCVS
  SISCCIDPLIYYYASSECQRYVYSILCCKESSDPSSYNSSGQLMASKMDTCSSNLNNSIY
  KKLLT
• Function: May play a role in platelets activation and in vascular development. High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Endocytosis (hsa04144)
  PI3K-Akt signaling pathway (hsa04151)
  Complement and coagulation cascades (hsa04610)
  Platelet activation (hsa04611)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Peptide ligand-binding receptors (R-HSA-375276)
  G alpha (q) signalling events (R-HSA-416476)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vorapaxar	DMA16BR	Myocardial infarction	BA41-BA43	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E5555	DMQERC6	Acute coronary syndrome	BA41	Phase 2	[2]
PZ-128	DMU5H3A	Peripheral arterial occlusive disorder	BD4Z	Phase 2	[3]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-171113	DMIQB9E	Thrombosis	DB61-GB90	Terminated	[4]
RWJ-58259	DMYXD6A	Artery stenosis	BD52	Terminated	[5]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RWJ-56110	DME07AN	Discovery agent	N.A.	Investigative	[6]
SCH-205831	DM584T6	Thrombosis	DB61-GB90	Investigative	[7]
SCH-602539	DMRDM9S	Arteriosclerosis	BD40	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	4.89E-02	-0.32	-0.77

References

• [1] In Process Citation. Pharm Unserer Zeit. 2009;38(4):320-8.
• [2] Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin-Acute Coronary Syndromes Trial. Circulation. 2011 May 3;123(17):1843-53.
• [3] PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2990-3003.
• [4] In vitro antiplatelet profile of FR171113, a novel non-peptide thrombin receptor antagonist. Eur J Pharmacol. 1999 Nov 19;384(2-3):197-202.
• [5] RWJ-58259: a selective antagonist of protease activated receptor-1. Cardiovasc Drug Rev. 2003 Winter;21(4):313-26.
• [6] Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62.
• [7] Himbacine derived thrombin receptor (PAR-1) antagonists: SAR of the pyridine ring. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4509-13.
• [8] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 347).